Abstract
INTRODUCTION
The availability of amyloid beta (Aβ) targeting therapies for Alzheimer’s disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.
METHODS
We evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer’s Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.
RESULTS
Plasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816–0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.
DISCUSSION
Lumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.
Highlights
Lumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid positivity.
Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ42/Aβ40 over time.
Plasma Aβ42/Aβ40 predicted future cognitive decline across the Alzheimer’s disease (AD) spectrum.
Plasma Aβ42/Aβ40 was sensitive to memory and tau burden in clinically unimpaired older adults.
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This post is Copyright: Alexandra N. Trelle,
Christina B. Young,
Hillary Vossler,
Javier Ramos Benitez,
Karly A. Cody,
Justin H. Mendiola,
Michelle S. Swarovski,
Yann Le Guen,
Igor Feinstein,
Robert R. Butler III,
Divya Channappa,
America Romero,
Jennifer Park,
Marian Shahid‐Besanti,
Nicole K. Corso,
Kelly Chau,
Amanda N. Smith,
Irina Skylar‐Scott,
Maya V. Yutsis,
Carolyn A. Fredericks,
Lu Tian,
Kyan Younes,
Geoffrey A. Kerchner,
Gayle K. Deutsch,
Guido A. Davidzon,
Sharon J. Sha,
Victor W. Henderson,
Frank M. Longo,
Michael D. Greicius,
Tony Wyss‐Coray,
Katrin I. Andreasson,
Kathleen L. Poston,
Anthony D. Wagner,
Elizabeth C. Mormino,
Edward N. Wilson | December 23, 2024